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Evaluation of adherence to national treatment guidelines among tuberculosis patients in three provinces of South Africa J V Ershova,1,2 PhD, MS, MPH; L J Podewils,1 MS, PhD; L E Bronner,1 MPH; H G Stockwell,2 ScD; S Dlamini,3 MPH, MA; L D Mametja,3 MPH Division of Tuberculosis Elimination, Centers for Disease Control and Prevention, Atlanta, Georgia, USA College of Public Health, University of South Florida, Tampa, Florida, USA 3 Tuberculosis Control and Management, National Department of Health, Pretoria, South Africa 1 2
Corresponding author: J V Ershova (
[email protected]) Background. Standardised tuberculosis (TB) treatment through directly observed therapy (DOT) is available in South Africa, but the level of adherence to standardised TB treatment and its impact on treatment outcomes is unknown. Objectives. To describe adherence to standardised TB treatment and provision of DOT, and analyse its impact on treatment outcome. Methods. We utilised data collected for an evaluation of the South African national TB surveillance system. A treatment regimen was considered appropriate if based on national treatment guidelines. Multivariate log-binomial regression was used to evaluate the association between treatment regimens, including DOT provision, and treatment outcome. Results. Of 1 339 TB cases in the parent evaluation, 598 (44.7%) were excluded from analysis owing to missing outcome or treatment information. The majority (697, 94.1%) of the remaining 741 patients received an appropriate TB regimen. Almost all patients (717, 96.8%) received DOT, 443 (59.8%) throughout the treatment course and 274 (37.0%) during the intensive (256, 34.6%) or continuation (18, 2.4%) phase. Independent predictors of poor outcome were partial DOT (adjusted risk ratio (aRR) 3.1, 95% confidence interval (CI) 2.2 - 4.3) and previous treatment default (aRR 2.3, 95% CI 1.1 - 4.8). Conclusion. Patients who received incomplete DOT or had a history of defaulting from TB treatment had an increased risk of poor outcomes. S Afr Med J 2014;104(5):362-368. DOI:10.7196/SAMJ.7655
According to the World Health Organization (WHO), South Africa (SA) was one of five countries with the highest TB incidence in 2011, estimated at 500 000 new TB cases and approximately 25 000 deaths.[1] In 2009 the South African National Tuberculosis Programme (NTP) released new national tuberculosis management guidelines for healthcare personnel and managers.[2] The guidelines include treatment strategies suggested by the WHO and recommend that all patients receive directly observed therapy (DOT) for the entire treatment course. However, despite NTP efforts to improve access to treatment and treatment adherence among TB patients, the proportion with successful treatment outcomes remains low (79% v. target of 86% cured or completed treatment) and mortality rates remain high (49/100 000).[1] Patients in whom treatment fails or who do not complete treatment are at risk for acquisition of drug-resistant TB, additional morbidity, and mortality. A patient’s ability to adhere to TB treatment is a complex, dynamic phenomenon with a wide range of factors impacting on treatmenttaking behaviour. Non-adherence to assigned treatment has been cited as the major barrier to TB control worldwide.[3-8] Although DOT has been well documented to improve patient adherence to TB treatment and optimise treatment outcomes,[4-6] studies have reported that DOT coverage remains low in many parts of the world, including SA.[3-6] A study conducted in the North West Province of SA found that the proportion of TB patients receiving DOT was as low as 56.8%, with coverage lowest among TB retreatment patients,[5]
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while another in KwaZulu-Natal reported that only 43 of 70 priority facilities (61%) had a DOT programme.[6] Furthermore, although countries have implemented the WHOrecommended directly observed, short-course (DOTS) strategy[7] that includes DOT along with four other components, individual healthcare workers (HCWs) may not be aware of or fully informed about the strategy, may not be willing to implement it, or may not have the resources to implement it. Studies have reported that not all HCWs have been exposed to the national TB treatment guidelines, and many are not prescribing recommended regimens.[8-10] A 2012 systematic review that included 31 studies from 14 countries cited wide variation in HCW knowledge of treatment regimens (8 - 100%) and treatment duration (5 - 99%).[11] According to another recent review, inappropriate treatment regimens were often prescribed to patients (in 67% of 37 studies included in the review), with the proportion of patients on inappropriate treatment regimens ranging between 0.4% and 100%.[12] In SA, while several studies evaluating DOT have been conducted,[5-6] the effect on treatment outcomes of failing to adhere to guidelines for standard treatment regimens and DOT has not been investigated previously. Knowledge of the impact of non-adherence to standard regimens and DOT on treatment outcomes will allow programmes and clinicians to recognise practices essential to treat and manage patients with TB effectively. We aimed to describe treatment management practices in three SA provinces, including assignment of treatment regimen and DOT
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coverage for TB patients; evaluate treatment regimen practices and DOT coverage in the context of national TB treatment guidelines; and assess the impact of failing to adhere to standard treatment regimens and DOT on TB treatment outcomes.
Methods
We conducted a secondary analysis of data collected as part of a parent project aimed at evaluating the TB surveillance and electronic tuberculosis registry (ETR) in SA.[13] The parent project included 1 339 patients diagnosed with TB in the first quarter of 2009 in Gauteng, KwaZulu-Natal and Mpumalanga provinces. Information on key TB variables was abstracted onto standardised forms from multiple data sources, including the patient treatment card, the paper TB register at the health facility, and the ETR[14] at the sub-district (initial), district, provincial and national levels. Owing to missing information in the ETR at these district, provincial and national levels, the current analysis was restricted to the three initial data sources: patient treatment card, TB register and initial ETR. We used the following decision rules to resolve discrepant information from the multiple data sources: (i) if there was information in all 3 data sources, we accepted the variable value reflected in 2 of 3 sources; (ii) if 3 or 2 data sources had a value available but all had different values, the value in the TB register was used; and (iii) if only 1 data source had information available, we took the value from this source. Our analysis included all TB patients in the parent project for whom information was available on TB treatment regimen, DOT coverage, and treatment outcome in at least one data source. All cases with missing information on TB treatment regimen, DOT coverage or treatment outcome and those who moved or transferred out during the current treatment episode were excluded. Treatment regimens were categorised as appropriate or inappropriate based on national guidelines.[2] The guidelines include WHO-recommended treatment strategies for new patients (regimen 1), retreatment patients (regimen 2) and children (regimen 3).[2] Adults and children aged 8 years and older with no history of a previous TB episode who were prescribed standard therapy (regimen 1) were considered to be on appropriate therapy; all other regimens for these patients were classified as inappropriate. Regimen 2 was considered appropriate for retreatment patients, and regimen 3 was considered to be appropriate for children younger than 8 years of age; other regimens prescribed for these patient
groups were considered inappropriate. DOT adherence was categorised as full for those who received DOT during the entire course of TB treatment (100% of doses through DOT), partial for patients receiving DOT during either the intensive or the continuation phase, and no DOT for patients who were not provided any DOT during treatment. Death, treatment failure and default were considered poor TB treatment outcomes; cure and treatment completion were considered successful outcomes. Risk ratios (RRs) and 95% confidence intervals (CIs) were used to measure the effect of adherence to standard treatment regimens and DOT on treatment outcomes. Univariate associations were further examined to identify potential confounders and effect modifiers. A multivariate log-binomial regression model was developed to identify independent predictors of poor treatment outcome among TB patients. Variables with an established biological plausibility based on previous research or that were significant based on a cut-off of p≤0.05 were retained in the final model.
Ethical considerations
Since data collection was a part of routine TB control efforts, individual patient consent or parental assent was not required. All data were safeguarded to protect patient confidentiality and no individual patient identifiers were retained in the study database. Participation of the US Centers for Disease Control and Prevention (CDC) and the South African National Department of Health in this project did not meet the definition of engagement in research on human subjects because the investigators did not interact with study subjects or have access to patient identifiable data, so separate institutional review board approval was not required. A formal written waiver for the need for ethics approval was issued by the CDC/DTBE associate director of science.
Results
Of 1 339 patients in the parent project, 598 (44.7%) were excluded owing to missing information on final treatment outcome (n=130), DOT coverage (n=213) or both
Records collected in the database 1 339 (100%)
382 (28.5%) excluded – missing treatment outcome
Records with treatment outcome available 957 (71.5%)
213 (15.9%) excluded – missing DOT
Records with treatment outcome and DOT available 744 (55.6%)
3 (0.2%) excluded – missing treatment regimen
Records with treatment outcome, DOT and treatment regimen 741 (55.3%)
Fig. 1. Selection of patient population (DOT = directly observed therapy).
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Table 1. Sociodemographic and clinical characteristics of the patient population
Characteristics
All collected cases (N=1 339) n (%)
Analytic cohort (N=741) n (%)
Excluded cases (N=598) n (%)
Gender
p-value* 0.98
Male
720 (53.8)
399 (53.9)
321 (53.8)
Female
617 (46.2)
341 (46.1)
276 (46.2)
